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A histone mimic links DNA replication and DNA methylation maintenance

Dr Pierre-Antoine DEFOSSEZ
CNRS UMR7216, Université Paris 7, France

vendredi 01 septembre 2017 - 11h00 - Auditorium, IGBMC
Invité(e) par Génomique fonctionnelle et cancer, Hinrich GRONEMEYER

DNA methylation is an essential epigenetic mark in mammals, and its
has to be re-established after each round of DNA replication. The
protein UHRF1 is essential for this process; it is proposed to target
newly replicated DNA by cooperatively binding hemimethylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered.
Here we present evidence for a direct recruitment of UHRF1 by the
replication machinery, via DNA Ligase 1 (LIG1). A histone H3K9-like
mimic within LIG1 is methylated by G9a and GLP, and binds UHRF1 more avidly than H3K9me2/3 does. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. These results further elucidate the function of UHRF1, identify a new non-histone target of G9a and GLP, and provide the first example of a histone mimic that coordinates DNA replication and DNA methylation maintenance.

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